title: Dendritic cells pulsed with CEA peptide induce CEA-specific CTL with restricted TCR repertoire.
abstract: The human carcinoembryonic antigen (CEA), which is expressed in several cancer types is a potential target for antigen-specific immunotherapy. In this study, we show that dendritic cells (DC) pulsed with an HLA class I restricted CEA cytotoxic T lymphocyte (CTL) peptide epitope can stimulate T cells to kill CEA peptide loaded T2 target cells as well as CEA expressing tumor lines in the presence of interleukin-7 (IL-7) in an HLA-restricted manner. This has been demonstrated for carcinoma patients as well as healthy donors. The DC-CEA + IL-7 stimulated cultures contained predominantly CD3+CD8+CD56- cells indicative of MHC class I restricted CTL. In addition, DC-CEA + IL-7 stimulated cells showed higher levels of CD69 expression compared with cells stimulated with IL-7 alone, implying an activated phenotype. When the T-cell receptor (TCR) from CTL cultures stimulated with DC-CEA + IL-7 was analyzed, an oligoclonal pattern of expression was found for certain V beta subfamilies compared with the polyclonal patterns shown by IL-7 or phytohemagglutinin stimulated T cells from the same donors. This TCR restriction appeared to be maintained and enhanced after additional rounds of restimulation with DC-CEA + IL-7. The association between cytotoxicity and TCR restriction suggests that TCR analysis may be useful as an in vitro indicator to monitor alterations in the T-cell population in response to antigen-specific immunotherapies.
authors.affiliation: RPR GenCell, Santa Clara, California 95054-1114, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Alters
authors.forename: J R
authors.initials: JR
authors.lastname: Gadea
authors.forename: M
authors.initials: M
authors.lastname: Sorich
authors.forename: G
authors.initials: G
authors.lastname: O'Donoghue
authors.forename: S
authors.initials: S
authors.lastname: Talib
authors.forename: R
authors.initials: R
authors.lastname: Philip
mesh_terms: D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D002272:Carcinoembryonic Antigen; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D015851:Interleukin-7; D010446:Peptide Fragments; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell